This project is designed to explore the possibility that patients with positive coronary angiograms who have a strongly positive family history of coronary heart disease but do not have the usual risk factors, may develop atherosclerosis primarily because of some cellular defect resulting in arterial cholesteryl ester accumulation. The binding, internalization and degradation of LDL, the effects of LDL binding on acyl-cholesterol acyltransferase and lysosomal cholesteryl ester hydrolase as well as on cholesteryl ester accumulation will be determined in skin fibroblast cell lines developed from these patients and compared with the results obtained in normal skin fibroblasts using tissue culture techniques. A method for quantitating the removal of prelabeled cholesteryl esters from fibroblasts will be standardized and also utilized in these studies. Particular emphasis will be placed on determining whether or not abnormalities of cellular cholesteryl ester removal may play a role in atherogenesis in normal lipemic individuals.